Phenotypes Associated with This Genotype

Genotype
MGI:6111393

• Allelic Composition: Tg(Ins2-IAPP)L13Gjsc/0
• Genetic Background: FVB/N-Tg(Ins2-IAPP)L13Gjsc

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

abnormal homeostasis ( J:142009 )

• 96% of mice develop diabetes, with a mean onset time of 11.2 weeks

decreased insulin secretion ( J:142009 )

hyperglycemia ( J:142009 )

• mice develop hyperglycemia from 6 weeks after birth and blood glucose remains elevated throughout the 31 week monitoring period

increased circulating glucagon level ( J:142009 )

• plasma glucagon is increased at the end-diabetic stage

decreased circulating insulin level ( J:142009 )

• plasma insulin is decreased at the end-diabetic stage but is normal at mid-diabetic stage

impaired glucose tolerance ( J:142009 )

• intraperitoneal glucose tolerance tests in fasted animals at the mid-diabetic stage shows impaired glucose tolerance and elevated fasting blood glucose

• however, systemic insulin administration at the mid-diabetic stage shows that mice are more responsive to insulin, indicating absence of peripheral insulin resistance and ex vivo glucose uptake in isolated soleus muscle is normal

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:142009 )

• beta-cell secretory granules are lacking in islets at the end-diabetic stage

• however, islet amyloid formation is not observed

decreased pancreatic beta cell mass ( J:142009 )

• beta cell loss during diabetes progression resulting in a decrease in beta cell mass

decreased pancreatic beta cell number ( J:142009 )

• decrease in beta cell numbers at the end-diabetic stage

abnormal pancreas physiology ( J:142009 )

• pancreatic human amylin and hence, total amylin, is elevated before diabetes development

• pancreatic glucagon is elevated at the end-diabetic stage

• mouse amylin levels are elevated before diabetes onset, however, pancreatic mouse amylin concentrations are decreased at the mid- and end-diabetic stages

• pancreatic insulin levels are decreased at mid- and end-diabetic stages

abnormal pancreatic beta cell physiology ( J:142009 )

• progressive decline in beta cell function

increased pancreatic beta cell apoptosis ( J:142009 )

• beta-cells from end-stage diabetic mice frequently exhibit invagination of their nuclear membranes and chromatin margination, characteristics of apoptosis

• number of apoptotic islet cells are increased at the mid-diabetic stage

increased amylin secretion ( J:142009 )

• mice exhibit increased release of human amylin from the pancreas into the plasma

decreased insulin secretion ( J:142009 )

cellular

increased pancreatic beta cell apoptosis ( J:142009 )

• beta-cells from end-stage diabetic mice frequently exhibit invagination of their nuclear membranes and chromatin margination, characteristics of apoptosis

• number of apoptotic islet cells are increased at the mid-diabetic stage

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:142009